Background: Saphenous vein grafts (SVGs) are broadly used in coronary artery bypass grafting despite their inferior patency compared with arterial grafts. Recently, the no‐touch technique (NT), in which an SVG is harvested with a pedicle of perivascular adipose tissue (PVAT) without conduit distension, was shown to improve long‐term patency compared with conventional preparation (CV), wherein outer tissue is removed with distension. The NT was also reportedly associated with reduced atherosclerosis. Although endothelial damage provoked by conventional distension may underlie poor patency when CV is performed, the precise mechanisms underlying the salutary effects of the NT have been unclear. Methods and Results: Residual SVGs prepared with CV (CV‐SVGs) or NT (NT‐SVGs) were obtained during coronary artery bypass grafting. Nitric oxide (NO ₂ ⁻ /NO ₃ ⁻ (NO _x )) levels after 24 hours of tissue culture were quantified. The protein expression and localization were analyzed. The isometric force of SVG strips was measured. NT‐SVGs showed superior NO _x production to CV‐SVGs. PVAT generated the majority of NO _x in NT‐SVGs. PVAT highly expressed arginosuccinate synthase 1, a rate‐limiting enzyme in the molecular circuit for NO synthesis, thereby continuously providing the substrate for NO. A substantial level of endothelial NO synthase was also expressed in PVAT. Pharmacological inhibition of arginosuccinate synthase 1 or endothelial NO synthase significantly suppressed the NO _x production in NT‐SVGs. PVAT induced vasorelaxation through NO production, even in the endothelium‐denuded SVG strips. Conclusions: Preserving PVAT was predominantly involved in the superior NO _x production in NT‐SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT‐SVGs.

Elderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients. A total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan–Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey. The patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group. Surgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.

A 58-year-old Japanese female was referred to our hospital. Although the electrocardiogram showed ST elevation, coronary angiography showed intact coronary artery. We diagnosed Takotsubo cardiomyopathy and a left ventricular thrombus. Anticoagulation was administered; however, the left ventricular thrombus had become mobile and protrusive. We extirpated the left ventricular thrombus via trans-apical approach. Left ventricular thrombus is rare in Takotsubo cardiomyopathy, but these patients are at a higher risk of thromboembolism, especially if the thrombi are mobile and protruding.

Background: Although the maze procedure is an established surgical treatment for eliminating atrial fibrillation (AF), its efficacy in patients with mitral valve disease has remained unsatisfactory. A useful predictive marker for the outcome of the maze procedure is needed. The aim of this study was to investigate whether the preoperative ratio of atrial natriuretic peptide (ANP) to brain natriuretic peptide (BNP) reflects atrial fibrosis and can be used to predict the maze procedure outcome in patients with mitral valve disease. Methods: A total of 23 consecutive patients who underwent the radial approach to the maze procedure combined with mitral valve surgery were included in this study and were divided into a sinus rhythm (SR) group (n=16) and an AF group (n=7) based on postoperative cardiac rhythm. Plasma samples were obtained at rest before the operation and were analysed for ANP and BNP levels. Atrial tissue samples taken during surgery were used to quantify interstitial fibrosis. Results: The preoperative ANP-to-BNP ratio in the SR group was significantly higher than that in the AF group (0.74 +/− 0.29 vs. 0.42 +/− 0.28, respectively; p=0.025). Receiver operating characteristic (ROC) curve analysis was used to identify factors that predict outcomes after the maze procedure. The area under the ROC curve for the ANP-to-BNP ratio (0.81) was greater than for any other preoperative factors. Moreover, the preoperative ANP-to-BNP ratio demonstrated a negative correlation with left atrial fibrosis (r=−0.69; p=0.003). Conclusions: The preoperative ANP-to-BNP ratio can predict maze procedure outcome in patients with mitral valve disease, and it represents a potential biomarker for left atrial fibrosis.

To explore the impact of the no-touch harvesting technique on the vessel diameter of saphenous vein grafts. This retrospective, single-center study enrolled 166 patients who underwent isolated coronary artery bypass grafting using saphenous vein grafts. Saphenous vein grafts were harvested conventionally in 83 patients (conventional group) and using the no-touch technique in 83 patients (no-touch group). We analyzed graft patency and the vessel diameters of saphenous vein grafts in the pre- and postoperative states. The diameter mismatch between the saphenous vein grafts and the coronary artery at the anastomotic site was also measured; preoperative diameter was measured using ultrasound imaging, and the postoperative diameter was measured using electrocardiogram-gated enhanced computed tomography. A total of 135 saphenous vein grafts (66 and 69 grafts in the conventional and no-touch groups, respectively) were evaluated for postoperative patency. Graft patency was equivalent in the 2 groups (conventional, 96.9% vs no-touch, 100%; P = .24). A detailed evaluation was performed in 109 saphenous vein grafts (52 and 57 grafts in the conventional and no-touch groups, respectively). Saphenous vein graft diameter was significantly distended in the conventional group (preoperative, 2.6 ± 0.7 mm vs postoperative, 3.4 ± 0.5 mm; P < .0001). However, saphenous vein graft diameter did not change in the no-touch group (preoperative, 2.9 ± 0.4 mm vs postoperative 2.8 ± 0.4 mm, P = .33). The diameter mismatch was significantly smaller in the no-touch group (conventional 1.4 ± 0.6 mm vs no-touch 1.0 ± 0.4 mm, P < .0001). The no-touch technique avoids the expansion of graft diameter and diameter mismatch between the saphenous vein grafts and coronary artery.

In our previous study, we found that dry-preserved multilayered fibroblast cell sheets promoted angiogenesis and wound healing in a mouse ulcer model by releasing high levels of intracellular fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF), from dried cells. In the present study, to identify which cell types are suitable for human dry-preserved cell sheets (dry sheets), we compared the intracellular FGF2 levels in seven types of cells reported as cell sheets for clinical use or preclinical studies. FGF2 levels were high in mesenchymal cells, including human oral fibroblasts (HOFs) and human dermal fibroblasts (HDFs), human dental pulp stem cells (DPSCs), and human mesenchymal stem cells (MSCs); in contrast, FGF2 levels in human umbilical vascular endothelial cells (HUVECs), human skeletal muscle myoblasts (SkMMs), and human epidermal keratinocytes (HEKs) were remarkably low, approximately 25% those in fibroblasts. In addition, we prepared dry sheets from HOFs, DPSCs, and MSCs, and analyzed the growth factors released from each dry sheet upon rehydration. High levels of FGF2, HGF, and VEGF were detected in the eluate prepared by immersing each dry sheet. In particular, FGF2 and HGF were the most abundant in HOFs. An in vitro cell proliferation assay showed that these eluates significantly enhanced HUVEC proliferation compared to control cells. Furthermore, cells incubated with HOF eluate showed significantly higher cell proliferation than cells incubated with DPSC and MSC eluates. However, this proliferative response was significantly blocked by FGF2-neutralizing antibodies. These results demonstrate that growth factors released from human dry sheets have physiological activity and that this activity is mainly mediated by the effect of FGF2. Fibroblasts are ideal for the clinical application of dry-preserved cell sheets in humans owing to their high intracellular FGF2 content, fast cell proliferation, ease of handling, availability, and low culture costs, making them the most suitable cell source for regenerative medicine, with FGF2 release as the mechanism of action.